Within the context of chronic HIV infection, pulmonary arterial hypertension (PAH) is a life-threatening complication characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure and right heart failure. Lack of understanding of the pathogenesis of HIV-PAH, along with deficiencies of available animal models, greatly impede identification and testing of new therapies. In this proposal, the overall objectives will focus on 1) determination of the role of chronic immune activation and inflammation on the development of PAH in a non-human primate model of HIV-PAH and 2) the evaluation of the effectiveness of anti-retroviral therapy, conventional PAH therapy and anti-inflammatory therapy in the primate model. These studies will not only address the mechanisms associated with the development of HIV-PAH, but they will provide critical information regarding the timing and targets that may be amenable to therapies aimed at both prevention and resolution of vascular damage, hemodynamic alterations and right heart dysfunction.